By Alex Herman
LSD and other psychoactive drugs such as ketamine, psilocybin, DMT, and peyote (mescaline) have for many years held the interest of researchers and scientists throughout the world due to the striking effects that they have on the brain functions and behavior of many mammals. Psychiatric research in particular was initially drawn to the use of LSD (Lysergic acid diethylamide) as a drug that could produce model schizophrenia in test subjects and patients. There is a long history of psychedelics research correlated with schizophrenia ever since LSD and its counterparts proliferated in use during the 1960’s and 70’s (Snyder et al. 1974). In the mid 70’s, certain research conducted by Bowers and Freedman highlighted surprising similarities between the states of some early schizophrenic patients and the effects of psychedelic drugs (Snyder et al. 1974). Apparently, it was in the acute schizophrenic breakdowns of new patients that the researchers observed effects such as transcendence to new modes of perception and creativity. Also observed were experiences of both intense dread and elation, attitudes that are frequently alternated between in patients experiencing a psychedelic ‘trip’.
The relationships between psychedelics and schizophrenia are still being explored in today’s research, but now researchers are focusing in on the use of psychedelics as a model to test possible treatments for this debilitating mental disease. In early studies regarding neurotransmitters and schizophrenia, it was believed to be the abnormal levels and fluctuations of the neurotransmitters serotonin and dopamine that were primarily responsible for the diseases’ dramatic effects, but recent research on mice is uncovering a different culprit acting in the synapses of test subjects: the neurotransmitter glutamate. The so-called serotonin-glutamate complexes are under intense study made possible by the dosing of lab mice with nominal amounts of LSD and ketamine. Recent studies done by Stuart Sealfon and other researchers at the Mount Sinai School of Medicine in New York indicate that mice, when dosed with LSD, will experience behavior closely associated with schizophrenia in humans, due to uncontrolled regulation of serotonin receptors in neurons. These behaviors, however, are canceled out when a drug altering the glutamate receptors is given to the mice, indicating that glutamate transport and reception plays a much more important role in schizophrenia than we had originally thought.
In even more recent studies using the behavior of mice on psychoactives to model schizophrenia, findings suggest that the condition may actually be a result of glutamate hyperactivity as opposed to the original belief in hypoactivity (too much vs. too little activity). In this research, the lab rats used were genetically altered to ‘knockout’ (delete) the gene for the glutamate transporter EAAT1. This transporter has been “implicated in schizophrenia” as it is important in the removal of glutamate from in between cells and synapses. These ‘knockout’ mice were then given the NMDA glutamate receptor antagonist MK-801, which is a drug that stimulates an increase in the release of glutamate into the synaptic space. With an increase in glutamate and no way for the mice to regulate its distribution and transport, the effects produced in the behavior of the mice were striking. The mice displayed distinctly schizophrenic symptoms including hyperactivity, symptoms that have been closely associated with rats dosed with LSD and ketamine. It is true that these symptoms still do not make lab rats a paragon for modeling schizophrenia, especially in terms of the cognitive effects in humans, but they can still help to lead researchers towards new, more effective treatments.
The end game to all this recent research is that we are now on the path to finding more effective and useful treatments to combat the horrible effects of schizophrenia. The effects seen in the EAAT1 knockout mice can be helped through the use of glutamate-targeting drugs, and medicines are currently being developed of this persuasion for use as effective anti-psychotic treatments. The interplay between psychoactives, neurotransmitters, and schizophrenia is clearly helping to move medical research forward on a complex and debilitating mental disease.
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Rodvelt, K.R., Kracke, G.R., Schachtman, T.R., & Miller, D.K. (2008). Ketamine induces hyperactivity in rats and hypersensitivity to nicotine in rat striatal slices . Pharmacology Biochemistry and Behavior, 91, 71-76.
Snyder, S.H., Banerjee, S.P., & Yamamura, H.I. (1974). Drugs, neurotransmitters, and schizophrenia. Science. 184, 1243-1253.
Sealfon, Stuart (2008, February 25). LSD reveals schizophrenia treatment. Retrieved March 1, 2009, from news.com.au Web site: http://www.news.com.au/story/0,23599,23270344-23109,00.html
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